I. Tumor growth in mice with depressed capacity to mount inflammatory responses: possible role of macrophages.
Studies were made of the effects of various treatments on the growth in mouse feet of isografts of two methylcholanthrene-induced fibrosarcomas: C-4, of CBA/J mice, and A-2, of A/J mice. The isografts were prepared by pronase digestion of subcutaneous tumors and were injected as unseparated cell suspensions or as tumor-cell-enriched suspensions after depletion of infiltrating host inflammatory cells. The recipient mice were untreated or treated with reserpine, sublethal whole body irradiation, cyclophosphamide, or corticosteroids. Depletion of host cells from the inoculum resulted in increased growth from the same number of tumor cells. Reserpine treatment decreased the growth of both tumors, whether unseparated or tumor-cell-enriched, and whether injected into the foot or the flank. Irradiation, cyclophosphamide pretreatment, and corticosteroid pretreatment decreased the growth of normal inocula or enriched inocula or both. The effects of cyclophosphamide and corticosteroids were apparently not due to cytotoxicity to tumor cells. Normal resident peritoneal cells increased tritiated thymidine uptake by tumor cells in vitro. Sedimentation velocity separation showed the largest cells to be the most potent. It is suggested that some hot inflammatory reaction is necessary for optimal tumor growth and that murine hosts produce not only cells with antitumor effects but also cells, possibly a subpopulation of macrophages, that potentiate tumor growth.
D000818:Animals; D001772:Blood Cell Count; D001799:Blood Sedimentation; D003345:Corticosterone / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology*; D007110:Immunity, Active / Q000187:drug effects*; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008748:Methylcholanthrene / Q000009:adverse effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D011292:Premedication; D012110:Reserpine / Q000627:therapeutic use; D013997:Time Factors; D014271:Trifluridine / Q000032:analysis
D008748:Methylcholanthrene; D012110:Reserpine; D003520:Cyclophosphamide; D014271:Trifluridine; D003345:Corticosterone